Visualizing metabolic activity of tumor and immune cells with melanoma-bearing mice

A biomedical imaging team at the Morgridge Institute is exploring a new way to monitor metabolic reprogramming in cancer and immune cells – work that may ultimately lead to more precise cancer treatments.

Metabolic reprogramming is a key feature of cancer cells, which adapt their metabolism to fuel rapid reproduction in their tumor microenvironment. During tumorigenesis, immune cells can undergo similar changes that can affect their cancer combativeness.

Current models typically use cell isolation or other techniques, which diminishes the overarching spatial context and environment. However, this research calls attention to intravital optical metabolic imaging (OMI) as a technique that can provide single-cell imaging of metabolic changes using the fluorescence and lifetimes of NAD(P)H and FAD coenzymes in living organisms.

A new immunocompetent mouse model is used to study immune cells that express CD4 during their differentiation process or CD4 and/or CD8 when they reach maturity. This model is also equipped with mCherry, which essentially acts as a red fluorescent marker that enables scientists to track the immune cells in real time. This is significant since T cells are essential for recognizing and killing pathogens, including cancer, in our body.

Alexa Heaton
Alexa Heaton

“We now have this red label in all of the T cells and a subset of other immune cells,” says Alexa Heaton, lead author of a new study appearing this spring in the journal Frontiers of Oncology. “And so it actually allows us to do a lot of unique tests where we know exactly which cell population we’re looking at.”

Furthermore, the researchers also developed a new code computation that assists in the automation of immune cell segmentation from these unique bio images that is now available via GitHub.

Heaton began working at the Morgridge Institute at the end of 2019, initially as a postdoc fellow. This project represents a collaboration between the Melissa Skala Lab at Morgridge and Paul Sondel Lab at the UW–Madison Department of Human Oncology. Heaton says the project is a good example of what kind of important work can be done when an institution fosters and supports cross-functional expertise.

Beyond the insight this imaging approach provides into tumor and immune cell metabolism, it also is quite promising in the realm of advancing immunology and immunotherapy as a whole. Studying metabolic heterogeneity, especially in living organisms, can help researchers build their understanding of these cell interactions surrounding cancer progression as well as propel them to the development of more effective and personalized cancer treatments.

“We feel like this immunotherapy piece is really important to get more at these healthier, safer options for patients and to have them be more targeted instead of just going after all of the healthy cells too,” says Heaton. “In order to better develop those kinds of therapies, we really need to know which immune cells are taking part and are really interested in asking how that affects the dynamics.”